Sympathetic neural and humoral stimuli influence coronary vascular resistance directly through effects on coronary vessels and indirectly through effects on the myocardium. Although animal studies suggest that the indirect dilator effects of sympathetic stimulation usually overshadow direct constrictor effects, recent work has shown that direct effects can play a dominant role in control of coronary vascular resistance. Information on neural control of coronary vascular resistance in humans is limited and has been difficult to obtain primarily for methodological reasons. We have recently developed and validated a small intralumenal Doppler catheter which can measure phasic coronary blood flow velocity in conscious humans. We will utilize this catheter to study coronary blood flow velocity in response to reflex and direct sympathetic stimuli asking three questions: 1) Is the neurogenic constrictor response accentuated in the presence of hypercholesterolemia without significant coronary lesions? 2) Is this response accentuated in the presence of coronary atherosclerosis? 3) Does beta blockade unmask accentuated adrenergic coronary vasoconstriction in patients with coronary lesions? Using the coronary blood flow velocity response to intracoronary papaverine as a measure of selective vasodilator reserve and quantitative coronary angiography to assess lesion geometry, we will study vasodilator reserve, lesion geometry, and neural control of coronary blood flow velocity in normals and patients with coronary atherosclerosis. This methodology should allow us to obtain fundamental new insights into neural regulation of the coronary circulation in humans.